Proliferation control of kidney interstitial cells

ABSTRACTExpansion of interstitial cells in the adult kidney is a hallmark of chronic disease, whereas their proliferation during fetal development is necessary for organ formation. An intriguing difference between adult and neonatal kidneys is that the neonatal kidney has the capacity to control interstitial cell proliferation when the target number has been reached. In this study, we define the consequences of inactivating the TGFβ/Smad response in the interstitial cell lineage. We find that pathway inactivation through loss of Smad4 leads to over-proliferation of interstitial cells regionally in the kidney medulla. Genetic and molecular interaction studies showed that Smad3/4 participates in the Wnt/β-catenin signaling pathway, which is responsible for promoting proliferation of interstitial cells. Specifically, Smad4 is required for the expression of the Wnt feedback inhibitor Apcdd1, and based on these findings we propose a model for interstitial cell proliferation control in which the Wnt/β-catenin proliferative signal is attenuated by TGFβ/Smad signaling to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.Summary statementThis study describes a novel function for TGFβ signaling in the developing renal interstitium. Mice with Foxd1-Cre-mediated deletion of Smad4 have interstitial expansion and activated Wnt signaling.

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Smad4 controls proliferation of interstitial cells in the neonatal kidney

Development ◽

10.1242/dev.199984 ◽

2021 ◽

Author(s):

Sarah S. McCarthy ◽

Michele Karolak ◽

Leif Oxburgh

Keyword(s):

Interstitial Cell ◽

Cell Lineage ◽

Interstitial Cells ◽

Tgfβ Signaling ◽

Target Number ◽

Kidney Medulla ◽

Pathway Activation ◽

Adult Kidney ◽

Neonatal Kidney ◽

Tgfβ Pathway

Expansion of interstitial cells in the adult kidney is a hallmark of chronic disease, whereas their proliferation during fetal development is necessary for organ formation. An intriguing difference between adult and neonatal kidneys is that the neonatal kidney has the capacity to control interstitial cell proliferation when the target number has been reached. In this study, we define the consequences of inactivating the TGFβ/Smad response in the interstitial cell lineage. We find that pathway inactivation through loss of Smad4 leads to over-proliferation of interstitial cells regionally in the kidney medulla. Analysis of markers for BMP and TGFβ pathway activation reveals that loss of Smad4 primarily reduces TGFβ signaling in the interstitium. While TGFβ signaling is reduced in these cells, marker analysis shows that Wnt/β-catenin signaling is increased. Our analysis supports a model in which Wnt/β-catenin mediated proliferation is attenuated by TGFβ/Smad to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.

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Tentacular and oral-disc regeneration in the sea anemone, Aiptasia diaphana

Development ◽

10.1242/dev.26.2.253 ◽

1971 ◽

Vol 26 (2) ◽

pp. 253-270

Author(s):

Irwin I. Singer

Keyword(s):

Electron Microscopy ◽

Cell Proliferation ◽

Cellular Proliferation ◽

Interstitial Cell ◽

Interstitial Cells ◽

Thymidine Uptake ◽

Cell Distribution ◽

Oral Disc ◽

Cellular Division ◽

Disc Regeneration

Autoradiography with [3H]thymidine and electron microscopy were used to determine (a) the patterns of cellular division exhibited by intact anemones, (b) if measurable increases in cellular proliferation accompany oral-disc regeneration, (c) whether interstitial cells are present in Aiptasia, and (d) if these cells could be responsible for the latter proliferative patterns. An oral-aboral gradient in cellular proliferation was exhibited by the epidermis of uncut anemones, with the highest levels in the tentacles. Wound healing did not require cell proliferation and did not immediately stimulatecellular division which was associated with subsequent morphogenetic events. Indices of presumptive oral-disc [3H]thymidine uptake into nuclei increased tenfold with the outgrowth of the new tentacles. This increase occurred in the epidermis, while only small amounts of gastrodermal proliferation were detected. It is hypothesized that the epidermis contributes new cells to the expanding gastrodermis during tentacle budding. Most of the [3H]thymidine-labeled nuclei were localized in the basal portions of the epidermis of intact anemones and 1- to 2-day-old regenerates; very few gastrodermal nuclei accumulated the label. Nests of interstitial cells and transforming interstitial cells were localized in the exact epidermal regions where nuclear labeling took place, suggesting that the proliferative patterns of intact and regenerating Aiptasia are a function of their interstitial cell distribution.

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Genetic analysis of developmental mechanisms in hydra. V. Cell lineage and development of chimera hydra

Journal of Cell Science ◽

10.1242/jcs.32.1.215 ◽

1978 ◽

Vol 32 (1) ◽

pp. 215-232

Author(s):

T. Sugiyama ◽

T. Fujisawa

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Interstitial Cell ◽

Cell Lineage ◽

Interstitial Cells ◽

Nerve Cells ◽

Polyp Size ◽

Primary Determinant ◽

One Year ◽

Almost All

Chimeric hydra were produced by making use of a strain (nf-1) which lacks interstitial cells, nerve cells and nematocytes. This strain arises by spontaneous loss of interstitial cells from its parental strain (sf-1) (Sugiyama & Fujisawa, 1978). Reintroduction of interstitial cells from other strains into nf-1 leads to the creation of chimeric strains that consisted of epithelial cells derived from strain sf-1 and interstitial cells and their derivatives (nerves and nematocytes) from other strains. In chimeras, interstitial or epithelial cells apparently maintain very stable cell lineages; no indication was obtained that suggested interstitial cell differentiation into epithelial cells or dedifferentiation in the opposite direction during the long courses of chimera cultures (up to one year). Developmental characters of chimeras were examined and compared to those of the epithelial cell (sf-1) and the interstitial cell donors. Almost all of the chimera's characters examined (growth rate, budding rate, tentacle numbers, polyp size, regenerative capacity, etc.) closely resembled those of the epithelial cell donor, but not of the interstitial cell donors. This suggests that epithelial cells, rather than interstitial or nerve cells, are the primary determinant of most, if not all, of hydra developmental characters.

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A large-scale study of Yap1p-dependent genes in normal aerobic and H2O2-stress conditions: the role of Yap1p in cell proliferation control in yeast

Molecular Microbiology ◽

10.1046/j.1365-2958.2000.01845.x ◽

2000 ◽

Vol 36 (4) ◽

pp. 830-845 ◽

Cited By ~ 31

Author(s):

Helene Dumond ◽

Nolwenn Danielou ◽

Moise Pinto ◽

Monique Bolotin-Fukuhara

Keyword(s):

Cell Proliferation ◽

Large Scale ◽

Stress Conditions ◽

Proliferation Control ◽

Large Scale Study ◽

Cell Proliferation Control

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Requirement for cell-proliferation control genes in Drosophila oogenesis.

Genetics ◽

10.1093/genetics/127.3.525 ◽

1991 ◽

Vol 127 (3) ◽

pp. 525-533

Author(s):

J Szabad ◽

V A Jursnich ◽

P J Bryant

Keyword(s):

Cell Proliferation ◽

Germ Line ◽

Follicle Cell ◽

Mitotic Recombination ◽

Follicle Cells ◽

Egg Development ◽

Proliferation Control ◽

Dominant Female ◽

Female Germ Line ◽

Cell Proliferation Control

Abstract Genes that are required for cell proliferation control in Drosophila imaginal discs were tested for function in the female germ-line and follicle cells. Chimeras and mosaics were produced in which developing oocytes and nurse cells were mutant at one of five imaginal disc overgrowth loci (fat, lgd, lgl, c43 and dco) while the enveloping follicle cells were normal. The chimeras were produced by transplantation of pole cells and the mosaics were produced by X-ray-induced mitotic recombination using the dominant female-sterile technique. The results show that each of the genes tested plays an essential role in the development or function of the female germ line. The fat, lgl and c43 homozygous germ-line clones fail to produce eggs, indicating a germ-line requirement for the corresponding genes. Perdurance of the fat+ gene product in mitotic recombination clones allows the formation of a few infertile eggs from fat homozygous germ-line cells. The lgd homozygous germ-line clones give rise to a few eggs with abnormal chorionic appendages, a defect thought to result from defective cell communication between the mutant germ-line and the nonmutant follicle cells. One allele of dco (dcole88) prevents egg development when homozygous in the germ line, whereas the dco18 allele has no effect on germ-line development. Fs(2)Ugra, a recently described follicle cell-dependent dominant female-sterile mutation, allowed the analysis of egg primordia in which fat, lgd or lgl homozygous mutant follicle cells surrounded normal oocytes. The results show that the fat and lgd genes are not required for follicle cell functions, while absence of lgl function in follicles prevents egg development.(ABSTRACT TRUNCATED AT 250 WORDS)

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